JP2020518661A - Benzimidazole compound and method for producing the same - Google Patents

Abstract

The present invention discloses a benzimidazole compound and a method for producing the same, and synthesizes various substituted benzimidazoles by SN2 and a cyclization reaction. , Ie, substitution of the fluorine atom with an amine by a one-pot reaction from the corresponding o-fluoroaryl-N,N-dimethylformamidine and a primary amine, followed by removal of dimethylamine and cyclization to give the product .. This method does not require the use of metal catalysts and/or toxic reagents, the method has unique selectivity and the reaction products are free of isomers.

Description

The present invention belongs to the technical field of organic synthesis and relates to a benzimidazole compound and a method for producing the same.

The benzimidazole ring system is one of many ubiquitous core structures used in drug discovery, and has already been discovered in many physiologically active compounds. For example, Raf (kinase inhibitor), LCK (lymphocyte-specific kinase inhibitor, etc.), serotonin receptor, phosphodiesterase IV antihistamine Astemizole 4 and antiulcer omeprazole.

Researchers have already made many efforts to develop and produce such compounds, and currently there are three main methods for synthesizing 1-substituted benzimidazole derivatives.
(a) Pathway 1: Condensation of 1,2-diaminoarene 1 with formic acid to form benzimidazole core 2 followed by direct N-alkylation on one nitrogen of the benzimidazole ring to give two regioisomers 3 And generate 4. However, in the majority of cases, regioselective alkylation on the designated nitrogen is difficult and the synthetic product in Procedure 1 contains a mixture of two regioisomers 3 and 4 (about 1:1 isomer). Exists. Separation and characterization of these mixtures is done by HPLC and 2D NMR techniques, which are time consuming and labor intensive processes.

(b) Route 2: Alkylation of 2-nitroaniline 5 and reduction of the nitro group to an amino group followed by cyclization of 7 with formic acid to form the required compound 3.

(c) Route 3: o-Fluoronitrobenzene Compound 8 is another precursor that produces Compound 3 in a three-step synthesis. The fluoro group of compound 8 is replaced with a primary amine (SN2), the nitro group is reduced to an amine and then cyclized with formic acid to produce the desired compound.

Taken together, these synthetic routes can now be time consuming and labor intensive, requiring purification of some intermediates, separation of regioisomers and characterization.

The present invention solves the above problems existing in the prior art, provides a benzimidazole compound, provides a method for producing the same, and synthesizes various substituted benzimidazole compounds by SN2 and a cyclization reaction. That is, the product was obtained by replacing the fluorine atom with an amine by a one-pot reaction from the corresponding o-fluoroaryl-N,N-dimethylformamidine and a primary amine, then removing the dimethylamine and cyclizing. obtain.

The technical method of the present invention is as follows.
A benzimidazole compound represented by the formula (I).
In the formula, R ₁ is —H, —Cl or an alkyl group.
R _{2 is, -NO 2, -F, -Cl,} Br, -CF 3, -CN, a -CO ₂ CH ₃ or -CO ₂ CH ₃ CH _2.
R ₃ is —H, an alkyl group, —CN or —CF ₃ .
R ₄ is —H, —Cl, an alkyl group, a cycloalkyl group or —CN.
R ₅ is —H, an alkyl group, a fluoroalkyl group, a cycloalkyl group, an aryl group or a heteroaryl group.
Y is, -CH, a _{-CH 2, -N, -NH, -NH} 2 , or a cycloalkyl group.

The manufacturing method of the benzimidazole type compound of this invention including the following steps.

A compound of formula (II) and a compound of formula (III), that is, o-fluoroaryl-N,N-dimethylformamidine and a primary amine are used as starting materials and reacted in a solvent to give a compound of formula (I), that is, benzimidazole. A compound is synthesized. The specific steps are as follows.
The definitions of the substituents R _{1 to} R ₅ and Y in the compound of formula (II) and the compound of formula (III) are the same as those of the compound of formula (I).

Further, in the above production method, the molar ratio of the compound of the formula (II) and the compound of the formula (III) is 1:1 to 12.

Furthermore, in the above production method, in the compound of formula (II), R ₂ is an electron-withdrawing group, and R ₂ is preferably —NO ₂ , —CF ₃ or —CN.

Further, in the above production method, the compound of formula (III) is a primary amine, preferably an aliphatic primary amine, an aromatic primary amine or a heterocycle-containing primary amine.

Further, in the above production method, the solvent is DMF, DMA, DMSO, HMPA, THF or dioxane.

Furthermore, in the said manufacturing method, the temperature of reaction is 80-220 degreeC, and time is 0.2-5h.

The beneficial effects of the present invention are specifically as follows. Various substituted benzimidazole compounds are synthesized by SN2 and cyclization reaction. That is, the product was obtained by replacing the fluorine atom with an amine by a one-pot reaction from the corresponding o-fluoroaryl-N,N-dimethylformamidine and a primary amine, then removing the dimethylamine and cyclizing. obtain. Compared with conventional methods, substitution and ring closure are completed in one pot, there is no need to use metal catalysts and/or toxic reagents in the reaction process, the synthetic method has unique selectivity, and the reaction products are isomers. The production is simple, the process flow is simple, and the yield is high.

In order to better understand the content of the present invention, the present invention will be further described by using the following examples.

In the present invention, unless otherwise specified, the room temperature is 25° C., and the stirring method with a limited number of rotations is a normal stirring method, and the number of rotations is 500 to 1000 rotations/minute.

Example 1
Magnetic stirring bar, dimethyl sulfoxide (DMSO) 15 mL, (E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine ((( E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine) 0.21 g (1 mmol) and cyclopropylamine 0.285 g (5 mmol) were added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 150° C. and kept for 2 hours. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 1-cyclopropyl-5-nitro-1H-benzo[d]imidazole (1-cyclopropyl-5-nitro- 0.115 g of 1H-benzo[d]imidazole) was separated. The yield was 57%.

¹ H NMR (500 MHz, MeOD) ppm 1.07-1.17 (m, 2H), 1.21-1.32 (m, 2H), 3.60 (dt, J = 7.02, 3.51Hz, 1H), 7.81-7.88 (m, 1H), 8.22-8.32(m,1H),8.45(s,1H),8.55(br.s.,1H); ¹³ C NMR(126MHz,MeOD)ppm 5.32,42.80,11.31,115.63,118.80,139.51,142.57,144.46 ,148.01; HRMS calcd.for C ₁₀ H ₉ N ₃ O ₂ :203.0695,found 203.0682.

Example 2
Magnetic stirring bar, dimethyl sulfoxide (DMSO) 15 mL, (E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine ((( E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine) 0.21 g (1 mmol) and cyclobutylamine 0.355 g (5 mmol) were added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 150° C. and kept for 2 hours. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 1-cyclobutyl-5-nitro-1H-benzo[d]imidazole (1-cyclopropyl-5-nitro-1H) was extracted from the mixture after distillation by silica gel column chromatography. 0.117 g of -benzo[d]imidazole) was isolated. The yield was 54%.

¹ H NMR (500 MHz, MeOD)) ppm 1.94-2.15(m,2H),2.51-2.73(m,4H),4.98-5.10(m,1H),7.72(d,J=8.85Hz,1H),8.20 (d,J=8.85Hz,1H),8.54(d,J=8.85Hz,2H); ¹³ C NMR (126MHz,MeOD)ppm 15.12,29.83,47.50,47.66,47.84,48.01,48.18,48.35,48.52, 48.63,48.66,50.46,111.27,115.61,118.50,137.66,142.76,144.22,145.75; HRMS calcd.for C ₁₁ H ₁₁ N ₃ O ₂ :217.0851,found 217.0838.

Example 3
Magnetic stirring bar, dimethyl sulfoxide (DMSO) 15 mL, (E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine ((( E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine) 0.21 g (1 mmol) and cyclobutylamine 0.355 g (5 mmol) were added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 160° C. and held for 3 hours. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 5-nitro-1-((tetrahydrofuran-2)methyl)-1H-benzo[d]imidazole (5- 0.192 g of nitro-1-((tetrahydrofuran-2-yl)methyl)-1H-benzo[d]imidazole) was isolated. The yield was 78%.

¹ H NMR (500 MHz, MeOD))ppm 1.56-1.71(m,1H),1.77-1.86(m,1H),1.86-1.96(m,1H),2.14(ddd,J=7.78,5.19,5.04Hz, 1H),3.69-3.78(m,1H),3.80-3.88(m,1H),4.23-4.32(m,1H),4.32-4.42(m,1H),4.54(dd,J=14.65,2.75Hz, 1H),7.82(d,J=8.85Hz,1H),8.25(dd,J=8.85,2.14Hz,1H),8.44(s,1H),8.57(d,J=2.14Hz,1H); 13C NMR (126MHz,MeOD))ppm 25.66,28.68,49.19,68.28,77.80,111.53,115.42,118.56,138.75,142.22,144.09,148.44; HRMS calcd.for C ₁₂ H ₁₃ N ₃ O ₃ :247.0957,found 247.0942.

Example 4
4-(3-(5-nitro-1H-benzo[d]imidazole)propyl)morpholine
4-(3-(5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine
Magnetic stirring bar, dimethylacetamide (DMSO) 15mL, (E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine ((( E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine) 0.21 g (1 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) were added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 160° C. and held for 3 hours. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 5-nitro-1-((tetrahydrofuran-2)methyl)-1H-benzo[d]imidazole (4- 0.246 g of (3-(5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine) was isolated. The yield was 85%.

¹ H NMR (500 MHz, MeOD) ppm 2.13 (t, J = 6.71 Hz, 2 H), 2.29-2.47 (m, 6 H), 3.65 (t, J = 4.73 Hz, 4 H), 4.48 (t, J = 6.71 Hz ,2H),7.83(d,J=9.16Hz,1H),8.28(dd,J=8.85,2.14Hz,1H),8.49(s,1H),8.60(d,J=2.14Hz,1H); ¹³ C NMR (126MHz, MeOD) ppm 26.11,43.38,47.50,47.67,47.84,48.01,48.18,48.35,48.52,53.60,55.28,66.77,111.11,115.58,118.61,138.35,142.47,144.15,148.13; HRMS calcd.for C ₁₄ H ₁₈ N ₄ O ₃ :290.1379,found 290.1381.

Example 5
Magnetic stirring bar, dimethylacetamide (DMSO) 15mL, (E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethyl in a 25mL single neck round bottom flask. Formamidine ((E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethylformamidine) 0.225 g (1 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) Was added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 170° C. and kept for 1 hour. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted three times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 4-(3-(6-methyl-5-nitro-1H-benzo[d]imidazol-1)propyl was obtained from the mixture after distillation by silica gel column chromatography. ) 0.216 g of morpholine (4-(3-(6-methyl-5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine) was isolated. The yield was 71%.

¹ H NMR (400 MHz, MeOD) ppm 2.11 (t, J = 6.65 Hz, 2 H), 2.33 (t, J = 6.78 Hz, 2 H), 2.35-2.44 (m, 4 H), 2.72 (s, 3 H), 3.62 -3.70(m,4H),4.42(t,J=6.78Hz,2H),7.66(s,1H),8.35(s,1H),8.38(s,1H); ¹³ C NMR(101MHz,MeOD)ppm 19.83,25.76,42.76,53.23,54.86,66.40,113.04,115.98,128.43,136.74,140.44,145.31,147.20; HRMS calcd.for C ₁₅ H ₂₀ N ₄ O ₃ :304.1535,found 304.1519.

Example 6
Magnetic stirring bar, dimethylacetamide (DMA) 15mL, (E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethyl in a 25mL single neck round bottom flask. Formamidine ((E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethylformamidine) 0.225 g (1 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) Was added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 170° C. and kept for 1 hour. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 6-methyl-5-nitro-1-(2-(pyrrole-1)ethyl)-1H-benzo[ was extracted from the mixture after distillation by silica gel column chromatography. 0.120 g of [d]imidazol-1(6-methyl-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole) was isolated. The yield was 44%.

¹ H NMR (500 MHz, MeOD) ppm 1.78 (br.s., 4H), 2.59 (br.s., 4H), 2.66 (s, 3H), 2.90-3.02 (m, 2H), 4.42 (t, J =6.71Hz,2H),7.58(s,1H),8.28(s,1H),8.35(s,1H); ¹³ C NMR (126MHz,MeOD)

ppm 20.18,23.45,44.30,47.50,47.68,47.85,48.02,48.19,48.36,48.53,54.11,54.98,113.25,116.38,128.90,137.04,140.86,145.72,147.55; HRMS calcd.for C ₁₄ H ₁₈ N ₄ O ₂ :274.1430,found 274.1415.

Example 7
6-methyl-5-nitro-1-(2-(pyrrole-1)ethyl)-1H-benzo[d]imidazole-1
6-methyl-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole
Magnetic stirring bar, dimethylacetamide (DMSO) 1.8mL, (E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethyl in a 2mL Biotage microwave reaction tube. Formamidine ((E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethylformamidine) 45 mg (0.2 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) Was added. After capping, the reaction mixture was heated to 160° C. in a Biotage microwave reactor for 15 minutes. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was placed in a 50 mL separating funnel containing 10 mL of water. The mixture was extracted 3 times with 5 mL ethyl acetate, the organic phases were combined, washed sequentially with saturated saline and water, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 6-methyl-5-nitro-1-(2-(pyrrole-1)ethyl)-1H-benzo[ was extracted from the mixture after distillation by silica gel column chromatography. 0.120 g of [d]imidazol-1(6-methyl-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole) was isolated. The yield was 48%.

¹ H NMR (500 MHz, MeOD) ppm 1.78 (br.s., 4H), 2.59 (br.s., 4H), 2.66 (s, 3H), 2.90-3.02 (m, 2H), 4.42 (t, J =6.71Hz,2H),7.58(s,1H),8.28(s,1H),8.35(s,1H); ¹³ C NMR (126MHz,MeOD)

ppm 20.18,23.45,44.30,47.50,47.68,47.85,48.02,48.19,48.36,48.53,54.11,54.98,113.25,116.38,128.90,137.04,140.86,145.72,147.55; HRMS calcd.for C ₁₄ H ₁₈ N ₄ O ₂ :274.1430,found 274.1415.

The technical method of the present invention is as follows.
A benzimidazole compound represented by the formula (I).

In the formula, R ₁ is —H, —Cl or an alkyl group.
R _{2 is, -NO 2, -F, -Cl,} Br, -CF 3, -CN, a -CO ₂ CH ₃ or -CO ₂ CH ₃ CH _2.
R ₃ is —H, an alkyl group, —CN or —CF ₃ .
R ₄ is —H, —Cl, an alkyl group, a cycloalkyl group or —CN.
R ₅ is —H, an alkyl group, a fluoroalkyl group, a cycloalkyl group, an aryl group or a heteroaryl group.
Y is, -CH ₂ -, - NH- or cycloalkylene group.

Example 4
4-(3-(5-nitro-1H-benzo[d]imidazole)propyl)morpholine
4-(3-(5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine

Magnetic stirring bar, dimethylacetamide ( DMA ) 15mL, (E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine ((( E)-N'-(2-fluoro-5-nitrophenyl)-N,N-dimethylformamidine) 0.21 g (1 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) were added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 160° C. and held for 3 hours. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed by a rotary evaporator, and the product 4-(3-(5-nitro-1H-benzo[d]imidazole)propyl)morpholine (4-( 0.246 g of 3-(5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine) was isolated. The yield was 85%.

Example 5


Magnetic stirring bar, dimethylacetamide ( DMA ) 15mL, (E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethyl in a 25mL single neck round bottom flask. Formamidine ((E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethylformamidine) 0.225 g (1 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) Was added. An one-neck round bottom flask was equipped with an air cooler. The reaction flask was placed in an oil bath, heated to 170° C. and kept for 1 hour. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was put into a 250 mL separating funnel containing 50 mL of water. The mixture was extracted 3 times with 30 mL ethyl acetate, the organic phases were combined, washed with saturated saline and water successively, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed on a rotary evaporator, and the product 4-(3-(6-methyl-5-nitro-1H-benzo[d]imidazol-1)propyl was obtained from the mixture after distillation by silica gel column chromatography. ) 0.216 g of morpholine (4-(3-(6-methyl-5-nitro-1H-benzo[d]imidazol-1-yl)propyl)morpholine) was isolated. The yield was 71%.

Example 7
6-methyl-5-nitro-1-(2-(pyrrole-1)ethyl)-1H-benzo[d]imidazole-1
6-methyl-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole

Magnetic stirring bar, dimethylacetamide ( DMA ) 1.8mL, (E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethyl in a 2mL Biotage microwave reaction tube. Formamidine ((E)-N'-(2-fluoro-4-methyl-5-nitrophenyl)-N,N-dimethylformamidine) 45 mg (0.2 mmol) and N-(3-aminopropyl)morpholine 0.355 g (7 mmol) Was added. After capping, the reaction mixture was heated to 160° C. in a Biotage microwave reactor for 15 minutes. After the reaction was stopped, the reaction flask was cooled to room temperature, and then the reaction mixture was placed in a 50 mL separating funnel containing 10 mL of water. The mixture was extracted 3 times with 5 mL ethyl acetate, the organic phases were combined, washed sequentially with saturated saline and water, and then dried over anhydrous sodium sulfate overnight. The ethyl acetate in the organic phase was removed with a rotary evaporator, and the product 6-methyl-5-nitro-1-(2-(pyrrole-1)ethyl)-1H-benzo[ was extracted from the mixture after distillation by silica gel column chromatography. 0.120 g of [d]imidazol-1(6-methyl-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole) was isolated. The yield was 48%.

Claims (9)

A benzimidazole compound represented by the formula (I).

(In the formula, R ₁ is -H, -Cl or an alkyl group. R ₂ is -NO ₂ , -F, -Cl, Br, -CF ₃ , -CN, -CO ₂ CH ₃ or -CO. ₂ CH ₃ CH _2. R ₃ is —H, an alkyl group, —CN or —CF _3. R ₄ is —H, —Cl, an alkyl group, a cycloalkyl group or —CN. ₅ is -H, an alkyl group, a fluoroalkyl group, a cycloalkyl group, an aryl group or a heteroaryl group, and Y is -CH, -CH ₂ , -N, -NH, -NH ₂ or a cycloalkyl group. is there.) The method for producing a benzimidazole compound according to claim 1, wherein the compound of formula (II) and the compound of formula (III), that is, o-fluoroaryl-N,N-dimethylformamidine and a primary amine are used as starting materials. And a step of reacting in a solvent to synthesize a compound of formula (I), that is, a benzimidazole compound, and a specific process is as follows: A method for producing a benzimidazole compound.
(The definitions of the substituents R _{1 to} R ₅ and Y in the formula (II) compound and the formula (III) compound are the same as those in the formula (I) compound.) 3. The production method according to claim 2, wherein the molar ratio of the compound of formula (II) and the compound of formula (III) is 1:1 to 12. 3. The production method according to claim ₂ , wherein R _{2 in the} compound of formula (II) is an electron-withdrawing group. The production method according to claim 4, wherein R ₂ is —NO ₂ , —CF ₃ or —CN. 3. The production method according to claim 2, wherein the compound of formula (III) is a primary amine. 7. The production method according to claim 6, wherein the compound of formula (III) is an aliphatic primary amine, an aromatic primary amine or a heterocycle-containing primary amine. 3. The production method according to claim 2, wherein the solvent is DMF, DMA, DMSO, HMPA, THF or dioxane. 3. The production method according to claim 2, wherein the reaction temperature is 80 to 220° C. and the time is 0.2 to 5 hours.